Breaking News
October 18, 2018 - Dietary fiber reduces brain inflammation during aging
October 18, 2018 - New tool could help prioritize recovery efforts for the poorest hit by natural disasters
October 18, 2018 - Hundreds of dietary supplements shown to contain unapproved drugs
October 18, 2018 - Active Pharmaceuticals ID’d in >700 Dietary Supplements
October 18, 2018 - Cell death protein also damps inflammation
October 18, 2018 - Health Highlights: Oct. 15, 2018
October 18, 2018 - Largest study of ‘post-treatment controllers’ reveals clues about HIV remission
October 18, 2018 - Bad Blood in Silicon Valley: A conversation with John Carreyrou
October 18, 2018 - ANTRUK’s Annual Lecture sends out message on shortage of funds for antibiotic research
October 18, 2018 - NAM special publication outlines steps to ensure interoperability of health care systems
October 18, 2018 - Novel method uses just a drop of blood to monitor effect of lung cancer therapy
October 18, 2018 - New blood test could spare cancer patients from unnecessary chemotherapy
October 18, 2018 - Training young researchers to work with data volumes arising in the health sector
October 18, 2018 - New Metrohm IC method is reliable and convenient to use for zinc oxide assay
October 18, 2018 - Global AIDS, TB fight needs more money: health fund
October 18, 2018 - Understanding the forces that cause sports concussions
October 18, 2018 - Research points to new target for treating periodontitis
October 18, 2018 - New tool improves assessment of postpartum depression symptoms
October 18, 2018 - From Biopsy to Diagnosis
October 18, 2018 - Sexual harassment and assault linked to worse physical/mental health among midlife women
October 18, 2018 - Stumped by medical school? A Q&A with a learning specialist
October 18, 2018 - Targeting immune checkpoints in microglia could reduce out-of-control neuroinflammation
October 18, 2018 - Study finds changes in antiepileptic drug metabolism during different trimesters of pregnancy
October 18, 2018 - Autonomic nervous system directly controls stem cell proliferation, study shows
October 18, 2018 - FDA Approves Talzenna (talazoparib) for gBRCAm HER2-Negative Locally Advanced or Metastatic Breast Cancer
October 18, 2018 - Sleeping Beauty technique helps identify genes responsible for NAFLD-associated liver cancer
October 18, 2018 - Many U.S. adults confused about primary care, study shows
October 18, 2018 - UC researcher focuses on light-mediated therapies to target breast cancer
October 18, 2018 - With philanthropic gifts, Stanford poised to make major advances in neurosciences | News Center
October 18, 2018 - Mice study shows antibiotics are not always necessary to cure sepsis
October 18, 2018 - Researchers discover why heart contractions are weaker in individuals with HCM
October 18, 2018 - Participation in organized sport during childhood may have long-term skeletal benefits
October 18, 2018 - Probiotic/antibiotic combination could eradicate drug-resistant bacteria
October 17, 2018 - More Socioeconomic Challenges for Hispanic Women With HIV
October 17, 2018 - 49,XXXXY syndrome – Genetics Home Reference
October 17, 2018 - Scientists uncover possible new causes of Tourette syndrome
October 17, 2018 - Girl undergoes unusual heart surgery after compassionate-use exemption | News Center
October 17, 2018 - Health Issues That Are Sometimes Mistaken for Gluten Sensitivity
October 17, 2018 - Elective induction of labor at 39 weeks may be beneficial option for women and their babies
October 17, 2018 - New smart watch algorithms can accurately monitor wearers’ sleep patterns
October 17, 2018 - Researchers demonstrate epigenetic memory transmission via sperm
October 17, 2018 - FDA, DHS announce memorandum of agreement to address cybersecurity in medical devices
October 17, 2018 - Health Tip: Know the Risks of Chicken Pox
October 17, 2018 - Immunotherapy effective against hereditary melanoma
October 17, 2018 - Researchers reveal new mechanism for how animal cells stay intact | News Center
October 17, 2018 - Alzheimer's Goes Under the Cryo-Electron Microscope
October 17, 2018 - Medicare for all? CMS chief warns program has enough problems already
October 17, 2018 - Metrohm Raman introduces Mira P handheld Raman system
October 17, 2018 - Expanding the knowledge about hippocampus to better understand cognitive deficits in MS
October 17, 2018 - Study of Nigerian breast cancer patients reveals prevalence of aggressive molecular features
October 17, 2018 - Many healthy children may have metabolic risk factors, finds study
October 17, 2018 - A new antibiotic could be a better, faster treatment for tuberculosis
October 17, 2018 - “I will not become a Robot Doctor”: A medical student vows to practice compassion
October 17, 2018 - Study findings may explain sporadic outbreaks of C. difficile infections in hospitals
October 17, 2018 - Purdue researchers develop new chemical process to find better drug ‘fits’ for patients
October 17, 2018 - Yale researchers develop way to attack RNA with small-molecule drugs
October 17, 2018 - New pragmatic study launched to understand the effectiveness of new type 2 diabetes drug
October 17, 2018 - Alnylam Announces Plan to Initiate Rolling Submission of a New Drug Application and Pursue Full Approval for Givosiran
October 17, 2018 - Nine cases of polio-like illness suspected in children in illinois
October 17, 2018 - Eisai enters into agreement with Eurofarma for development and sales of lorcaserin in 17 countries
October 17, 2018 - Patients once thought incurable can benefit from high-dose radiation therapy
October 17, 2018 - Researchers awarded grant to advance testing of experimental heroin vaccine
October 17, 2018 - Researchers examine SSRI use during pregnancy and major gestational malformations
October 17, 2018 - FDA grants Rare Pediatric Disease Designation for Immusoft’s Iduronicrin genleukocel-T
October 17, 2018 - Reliable Respiratory announces acquisition of Attleboro Area Medical Equipment
October 17, 2018 - Study reveals link between childhood abuse and higher arthritis risk in adulthood
October 17, 2018 - Research shows people over 65 are not performing enough physical activity
October 17, 2018 - FDA Approves Liletta (levonorgestrel-releasing intrauterine system) 52 mg to Prevent Pregnancy for up to Five Years
October 17, 2018 - Weight gain after smoking cessation linked to increased short-term diabetes risk
October 17, 2018 - Researchers find opportunity to control salt-sensitive hypertension without exercising
October 17, 2018 - Women not warned about cancer associated with breast implants
October 17, 2018 - Metrohm offers robust handheld Raman analyzer for Defense and Security
October 17, 2018 - Modeling Non-Numerical Data in Systems Biology
October 17, 2018 - Research aims to address health disparities in African-American men
October 17, 2018 - Human and cattle decoys trap outdoor-biting mosquitoes in malaria endemic regions
October 17, 2018 - High Circulating Prolactin Level Inversely Linked to T2DM Risk
October 17, 2018 - Study finds gene variant predisposes people to both Type 2 diabetes and low body weight
October 17, 2018 - Metrohm software products make it easy to comply with ALOCA and ALCOA+ guidelines
October 17, 2018 - Network of doctors identify the cause of 31 new conditions
October 17, 2018 - Notable improvement in brain cancer survival among younger patients but not much for elderly
Game theory can be used to identify potential flaws in current cancer treatment approaches

Game theory can be used to identify potential flaws in current cancer treatment approaches

image_pdfDownload PDFimage_print

Game theory can be utilized to identify potential flaws in current cancer treatment approaches and suggest new strategies to improve outcomes in patients with metastatic cancer, according to a new article published online today by JAMA Oncology. The study, which is authored by a mathematician, an evolutionary biologist and clinical physicians from Moffitt Cancer Center and Maastricht University, challenges the decades old standard of treatment for metastatic cancers in which drugs are typically administered continuously at the maximum-tolerated dose (MTD) until the tumor progresses.

The study shows that, by viewing cancer therapy as a game between the treating physician and the cancer cells, continuous administration of the same drug or drugs at MTD fails to exploit critical advantages possessed by the physician. Instead, the authors encourage oncologists to develop flexible strategic treatment plans. By exploiting his/her knowledge of the cancer’s evolutionary dynamics, the oncologist can continuously adjust drugs and doses to delay or prevent cancer progression caused by the evolution of resistance. With each adjustment, the oncologist updates information on the cancer’s response.

The Moffitt research team, led by Robert A. Gatenby, M.D., used mathematical modeling to investigate cancer treatment as a game played by the physician and cancer cells. In their study, the researchers demonstrate that the physician has two big advantages over his/her tumor opponents. First, the physician is rational while the cancer cells are not. This means that the physician, by understanding the principles of evolution, can plan ahead and anticipate the tumor cells’ response. Cancers, like all evolving organisms, can never anticipate the future and because of this are particularly vulnerable to changes in treatment by the physician. In addition, the physician has the advantage of always “playing” first – the cancer cells cannot begin to evolve resistance until the physician administers a therapy. This sequence of moves means that cancer treatment has a distinctive game theoretic form termed a “leader-follower” or “Stackelberg” game. Von Stackelberg was a German mathematician who extensively investigated the game dynamics in the mid-20th century. His work and that of several other game theorists have demonstrated that the leader in a Stackelberg gains a substantial advantage by using the first move to limit subsequent tumor responses. Furthermore, the leader can use fore-knowledge of the cancer to anticipate and steer its evolution and vulnerabilities.

“Current treatments for metastatic cancers, by giving the same drug repeatedly at the maximum tolerated dose, can inadvertently increase the speed with which cancer cells can evolve effective counter measures and then regrow,” said Gatenby, co-director of Moffitt’s Center of Excellence in Evolutionary Therapy. “Today, therapy is usually changed only when the tumor progresses. By using this strategy the physician cedes control to the cancer. Although standard practice for decades, administering drugs at maximum-tolerated dose until progression is rarely the optimal game theoretic strategy for metastatic cancers.”

“The current maximum-tolerated dose approach will only be successful if the cancer cell population is made up of similar cells that are unable to adapt and evolve quickly,” said Joel Brown, Ph.D., an evolutionary biologist at Moffitt. “That is rarely what we see for cancers that have widely metastasized. We can and must anticipate, steer and exploit the cancer cells’ evolutionary responses to our therapies.”

The study proposes changes in the standard treatment paradigms by encouraging physicians to better use their advantages as the sentient leader in their high-stakes game with the cancer. They can do this by continuously adjusting treatment and forcing the cancer cells to constantly change their response to unpredictable attacks from new drugs or combinations of drugs. The authors suggest that the physicians begin by precisely defining the goal of treatment. Is to cure the patient or is it to prolong life? This allows the physician to better balance the benefit of therapy against the potential toxicity and its effects on the patient’s quality of life. In a related suggestion, the authors suggest that the treating physician develops a strategy to deal with cancer cells that are resistant to therapy. If the goal is to cure, then resistant cells must be killed or prevented. If the goal is control, then physicians can use evolutionary principles to minimize the proliferation of resistant cells while limiting the toxicity of treatment. Finally, the physician, as the sentient player in the game, can continuously analyze the intratumoral evolutionary dynamics based on the tumor response during each treatment cycle. This information, often with the aid of a mathematical model, can provide information to improve the outcomes in subsequent cycles – a well-recognized approach in recursive games termed Bellman’s Principle.

To operationalize their theoretical study, the research team suggests precision medicine for metastatic cancers. In addition to using molecular techniques to identify treatment targets, precision medicine should integrate strategies to deal with the evolution of resistance which almost invariably leads to failure of even highly successful targeted therapies. The health team should design an explicit Resistance Management Plan (RMP) for each patient – an approach commonly used in pest management. They also recommend that the physician analyzes the outcomes of every patient, similar to After Action Reports (AAR) used in the military and disaster response teams. By learning from each individual patient, personalized oncology can itself evolve and improve over time.

While this approach is designed for incurable metastatic cancers, Katerina Stankova, Ph.D., a mathematician at Maastricht University and an expert on game theory, notes that the full dynamics of Stackelberg games have not yet been rigorously explored. “As we develop the mathematics in conjunction with cancer therapies, we expect that our analyses will uncover novel game-theoretic, evolutionary strategies that may increase the probability of curing even aggressive and heterogeneous cancers,” Stankova added.

Source:

https://moffitt.org/newsroom/press-release-archive/2018/new-study-views-cancer-treatment-as-a-game-to-find-strategies-that-improve-patient-outcomes/

Tagged with:

About author

Related Articles